The inhibition of female rabbit sexual behavior by progesterone: progesterone receptor-dependent and-independent effects.

In the pregnant domestic rabbit, scent marking ("chinning") and sexual behavior are inhibited by ovarian-derived progesterone (P). In order to distinguish behavioral effects of P that are PR-dependent from those mediated by its ring A reduced metabolites, we administered P, P+RU486 (PR antagonist), chlormadinone acetate (CA, synthetic progestin that does not form ring A reduced metabolites), or vehicle to ovariectomized (ovx) estradiol-benzoate (EB)-treated female rabbits, via sc injection, on experimental day 0. Chinning was quantified daily, and mating tests were done on days -1, 1, 3, 5, and 7. On day 1, chinning was significantly decreased, and the latency to be mounted by the male was significantly increased (indicating decreased sexual attractivity of the female) in P-treated females. The effect of P on chinning, but not its effect on sexual attractivity, was completely blocked by RU486 and replicated by CA. Although CA had no effect on attractivity on day 1, it decreased both sexual receptivity and attractivity on day 3. In a preference test in which the male could interact with either an ovx EB-treated female or an ovx female that had received one of the above hormone treatments 24 h earlier, P decreased sexual attractivity and increased aggression. The effect of P on aggression, but not its effect on attractivity, was blocked by RU486 and replicated by CA. These results indicate that both PR-dependent and PR-independent mechanisms decrease sexual attractivity, whereas PR activation is necessary for the inhibition of chinning and sexual receptivity, and for the stimulation of aggression.

Relevance of ovarian signaling for the early behavioral transition from estrus to pregnancy in the female rabbit.

During estrus, the female domestic rabbit (Oryctolagus cuniculus) displays scent marking behavior (chinning), which is immediately inhibited after mating, temporarily recovers, and then declines and remains inhibited across pregnancy. Chinning is inhibited by progesterone (P) and the activation of the progesterone receptor (PR), but it is unlikely that P participates in the "acute" (immediate) or "early" inhibition of chinning (24 to 96 h post-mating, before plasma P levels rise). Since PR is activated in a ligand-independent manner by a variety of signaling molecules, some of which (e.g., GnRH) are also associated with reflexive ovulation in this species, we hypothesized that neurochemical/neuroendocrine signals associated with mating activate PR, resulting in the inhibition of chinning. In Experiment 1, we tested whether the PR antagonist, RU486 (20 mg, injected s.c. at -1 h, or at -7 h and +3 h relative to mating) prevented the post-mating inhibition of chinning in intact females. RU486 did not prevent the post-mating decline in chinning, indicating that PR activation associated with mating is not necessary for this effect. In Experiment 2, we used ovariectomized (OVX), estradiol benzoate (EB)-treated females to test the hypothesis that ovarian signaling is necessary for the post-mating inhibition of chinning. The acute inhibition of chinning occurred in OVX females, but the early inhibition was absent. We conclude that ovarian signaling is necessary for the early, but not acute, post-mating inhibition of chinning. The PR seems not to participate in either of these phases.